Abstract

Iron–sulfur clusters are ancient cofactors that play a fundamental role in metabolism and may have impacted the prebiotic chemistry that led to life. However, it is unclear whether iron–sulfur clusters could have been synthesized on prebiotic Earth. Dissolved iron on early Earth was predominantly in the reduced ferrous state, but ferrous ions alone cannot form polynuclear iron–sulfur clusters. Similarly, free sulfide may not have been readily available. Here we show that UV light drives the synthesis of [2Fe–2S] and [4Fe–4S] clusters through the photooxidation of ferrous ions and the photolysis of organic thiols. Iron–sulfur clusters coordinate to and are stabilized by a wide range of cysteine-containing peptides and the assembly of iron–sulfur cluster-peptide complexes can take place within model protocells in a process that parallels extant pathways. Our experiments suggest that iron–sulfur clusters may have formed easily on early Earth, facilitating the emergence of an iron–sulfur-cluster-dependent metabolism.

  • Compound

    Fe2+- glutathione mononuclear complex

  • Compound

    [2Fe-2S] glutathione cluster

  • Compound

    [4Fe-4S] glutathione cluster

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Acknowledgements

The authors acknowledge the Simons Foundation (290360 to D.D.S., 290363 to J.W.S., 290362 to J.D.S., 290358 to S.S.M.), the Armenise-Harvard Foundation (to S.S.M.), COST action CM1304 (to C.B., J.D.S. and S.S.M.) and the University of Hull (to D.J.E. and S.Sh.) for funding. The authors thank L. Belmonte, C. Caumes, E. Izgu, E. Godino, N. Kamat, A. Mariani, T. Olsen, D. Rossetto, Z. Todd, O.D. Toparlak, A. Trifonov and M. Tsanakopoulou for discussions.

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Affiliations

  1. CIBIO, University of Trento, via Sommarive 9, 38123 Povo, Italy

    • Claudia Bonfio
    • , Luca Valer
    • , Simone Scintilla
    •  & Sheref S. Mansy
  2. Chemistry, School of Mathematics and Physical Sciences, University of Hull, Hull HU6 7RX, UK

    • Sachin Shah
    •  & David J. Evans
  3. Howard Hughes Medical Institute, Department of Molecular Biology, and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA

    • Lin Jin
    •  & Jack W. Szostak
  4. Department of Astronomy, Harvard University, 60 Garden Street, Cambridge, Massachusetts 02138, USA

    • Dimitar D. Sasselov
  5. MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK

    • John D. Sutherland

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Contributions

C.B., S.Sc., L.J., J.W.S., D.D.S., J.D.S. and S.S.M. designed the experiments. Photochemical studies, peptide synthesis and cluster stability were performed by C.B. and L.V. Mössbauer spectra were recorded and analysed by S.Sh. and D.J.E. The manuscript was written by C.B. and S.S.M. and edited by C.B., S.Sc., D.J.E., J.W.S., D.D.S., J.D.S. and S.S.M.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Sheref S. Mansy.

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DOI

https://doi.org/10.1038/nchem.2817

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